Nearly 8 billion gallons of wine are produced and consumed annually, a substantial fraction of which is red wine. Preliminary investigation suggests that many red wines contain high levels of direct-acting frameshift mutagens. There exists a strong epidemological correlation between the dose-dependent consumption of red wine and the occurrence of stomach cancer in France. The mutagenic load experienced by the global population from red wine consumption is clearly of significance to the environmental etiology of human cancer, particularly since the mutagenic compounds contained in wine are dissolved in 12-20% ethanol, itself a known promoter and carcinogen. The specific aims of this proposal are to: (1) determine the distribution and chemical identity of mutagenic compounds in red, rose, white, dessert wines and brandies; (2) define the production parameters which determine the level of mutagenic activity present in wine; and (3) devise procedures for the selective removal of mutagens from wine. Frameshift and base substitution mutagenic activity will be quantified by using the Ames Salmonella tester strain collection. Mutagenic activity in the presence and absence of microsomal, and fecal glycosidase, enzyme preparations will be determined. The influence of winery practices, including high pressure pressing of grapeskins, mechanically abrasive juice recirculation methods and fining treatments, on wine mutagenicity will be evaluated. Liquid chromatographic and HPLC techniques will be used to fractionate and purify mutagenic compounds from concentrated wine samples. The chemical identity of purified mutagens will be established by HPLC, UV-Vis spectra, NMR and MS techniques. The utilization of commercially available fining agents for the removal of wine mutagens will be evaluated in laboratory and winery scale studies.